• Somnath Bose, Lauren Kelly, Zachary Shahn, Lena Novack, Valerie Banner-Goodspeed, and Balachundhar Subramaniam.
• Department of Anesthesia, Critical Care and Pain Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts, USA.
• Acta Anaesthesiol Scand. 2022 Oct 1; 66 (9): 109911061099-1106.

BackgroundPolypharmacy of sedatives (PP) is a potentially modifiable, iatrogenic risk factor for ICU delirium. The extent to which sedative PP influenced development of high rates of delirium among critically ill COVID-19 patients is unknown. We tested the hypothesis that PP, defined as the use of four or more classes of intravenous agents, is a mediator in the causal pathway of mechanical ventilation and delirium.MethodsRetrospective cohort study of adults admitted with a primary diagnosis of RT-PCR+ for SARS-CoV2 to ICUs of a tertiary-level academic medical center between February 2020 and April 2021. Mediation analysis was conducted with bootstrap estimation to assess whether an association between mechanical ventilation and delirium was mediated by PP. Analyses were adjusted for potential confounders related to mechanical ventilation, mediator, and outcome, including age, gender, vasopressor use, median RASS scores, SOFA score within 24 h of admission, and maximum CRP levels.ResultsA total of 212 patients were included in the analysis. Of total patients, 72.6%(154/212) of patients had delirium (CAM-ICU+) during ICU stay. 54.7%(116/212) patients received PP. Mechanical ventilation (OR 3.81 [1.16-12.52]) and PP (OR 7.38 [2.4-22.68]) were identified as risk factors for development of ICU delirium after adjusting for prespecified confounders. PP acts as a mediator in the causal pathway between mechanical ventilation and delirium. 39% (95% CI: 17%-94%) of the effect of mechanical ventilation on delirium was mediated through PP.ConclusionPP mediates approximately 39% of the effect of mechanical ventilation on delirium, which is clinically and statistically significant. Studies should assess whether mitigating PP could lead to reduction in ICU delirium.Implication StatementPP of sedatives (defined as use of four or more intravenous agents) mediates approximately 39% of the effect of mechanical ventilation on development of ICU delirium. Avoidance of sedative PP may represent a viable strategy for reduction of ICU delirium.© 2022 Acta Anaesthesiologica Scandinavica Foundation.

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